Studies On The Synthesis Of Quinazoline Compounds Based On Cu-Catalyzed C-N Bond Formation

Quinazoline is an important nitrogen-containing heterocyclic compound,which widely exists in natural alkaloids,active drugs and functional materials.The existing methods for the synthesis of quinazolines have some disadvantages,such as low yield,harsh reaction conditions,cumbersome post-treatment and so on.Transition metal catalysis has the advantages of high reaction activity,high selectivity and less catalytic dosage.It is widely used in the field of synthesis of nitrogen heterocyclic compounds.Compared with noble metal catalysts,copper catalyst has more prominent advantages in the synthesis of quinazoline compounds,because not only the metal copper is cheap and easy to obtain,green,non-toxic and difficult to passivate,but also the copper catalyst has a variety of valence forms,which can realize a variety of catalytic paths through organic copper intermediates,so as to construct complex molecules from simple raw materials.Therefore,a new method for the synthesis of quinazoline compounds based on copper catalyzed C-N bond is proposed in this paper.The main content of this paper is divided into the following two parts:1.Study on copper catalyzed synthesis of quinazolinone compoundsA mild synthesis of quinazolinone compounds catalyzed by Cu（OTf）₂ from anthranilic acids and nitrile compounds was developed in this chapter.The optimum reaction conditions were established by optimizing the reaction conditions such as catalyst,additives,solvent and temperature.Under the optimal reaction conditions,more than 60 quinazolinones were obtained.The structures of all compounds were characterized by ¹H NMR,¹³C NMR and elemental analysis.The structures of compounds 2-4p were also confirmed by X-ray single crystal diffraction.The method is not only simple,mild reaction conditions,but also has good universality and wide application range.It is also suitable for synthesizing other natural alkaloids,such as schizocommunin.In addition,a preliminary study on the reaction mechanism for the synthesis of quinazolinones catalyzed by copper was proposed based on control experiments and theoretical analysis in this chapter.2.Study on copper catalyzed synthesis of tryptanthrin compoundsA one-pot synthesis of tryptanthrin and its derivatives catalyzed by CuI from isatins was developed in this chapter.The reaction was optimized by screening the reaction conditions such as catalyst,base,temperature and solvent,and the optimal reaction conditions were established.Under the optimal reaction conditions,34tryptanthrins were obtained.The structures of all compounds were confirmed by ¹H NMR,¹³C NMR and elemental analysis.The structure of natural product tryptanthrin was also confirmed by X-ray single crystal diffraction.This method not only has the advantages of simple operation,good selectivity and high yield,but also is suitable for the synthesis of a variety of tryptanthrin derivatives,such as natural alkaloid phaitanthrin A.In addition,a possible reaction mechanism was proposed tentatively based on the control experiments and characterization data.